Pfizer Inc announced positive top-line results from the phase 3 PALOMA-2 trial for Ibrance (palbociclib), an oral, first-in-class inhibitor of cyclin-dependent kinases (CDKs) 4 and 6.1 The study met its primary endpoint by demonstrating an improvement in progression-free survival (PFS) for the combination of Ibrance plus letrozole compared with letrozole plus placebo in post-menopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+, HER2-) advanced or metastatic breast cancer who had not received previous systemic treatment for their advanced disease.

The PALOMA-2 trial provides confirmatory evidence for Ibrance in combination with letrozole in the first-line setting, which was first studied in the Phase 2 PALOMA-1 trial. These data will support additional planned global regulatory submissions and a request for conversion of the accelerated approval for Ibrance to regular approval in the U.S. Detailed efficacy and safety results from PALOMA-2 will be submitted for presentation at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting.

“PALOMA-2 represents the third randomized study to demonstrate the benefit of Ibrance when added to hormonal therapy in the management of women with ER+, HER2- advanced breast cancer. Ibrance remains the only CDK 4/6 inhibitor with phase 3 data in this disease,” said Dr. Mace Rothenberg, MD, chief medical officer, Pfizer Oncology & senior vice president, Global Product Development, Oncology. “These results provide confirmatory evidence for PALOMA-1 and will be used to support regulatory submissions around the world, including a request for conversion of Ibrance from accelerated to full approval in the United States. We look forward to sharing the detailed results of PALOMA-2 with the oncology community and advancing our discussions with regulatory authorities.”

The adverse events observed with Ibrance in combination with letrozole in PALOMA-2 were generally consistent with the known safety profile for Ibrance across the different patient populations and lines of therapy in the clinical development program to date. The warnings and precautions of Ibrance include neutropenia, pulmonary embolism and embryo-fetal toxicity.

Since its introduction in February 2015, more than 25,000 women have been prescribed Ibrance by more than 6,000 prescribers in the US.

Based on the results of PALOMA-1, Ibrance first was approved by the US Food and Drug Administration (FDA) in February 2015 for the treatment of postmenopausal women with ER+, HER2- advanced breast cancer in combination with letrozole as initial endocrine-based therapy for their metastatic disease. The indication in combination with letrozole was approved under accelerated approval based on PFS. As stated at the time of the approval, continued approval for this indication may be contingent upon verification and description of clinical benefit in PALOMA-2, which the FDA identified as the confirmatory trial. Pfizer will work with the FDA to submit the results of PALOMA-2 to support conversion of the accelerated approval for Ibrance to regular approval in the US.

As previously announced in February 2016, Ibrance also is approved in the US for the treatment of hormone receptor-positive (HR+), HER2-advanced or metastatic breast cancer in combination with fulvestrant in women with disease progression following endocrine therapy based on results from the phase 3 PALOMA-3 study.

Ibrance also is approved in eight countries outside of the US, and Pfizer will work with additional global regulatory authorities to review the PALOMA-2 data. As previously disclosed in August 2015, Pfizer has filed a Marketing Authorisation Application (MAA) with the European Medicines Agency (EMA) for Ibrance in combination with endocrine therapy for the treatment of HR+, HER2- advanced or metastatic breast cancer. The MAA was based on the results from the PALOMA-1 and PALOMA-3 trials. Pfizer will work with the EMA to submit the PALOMA-2 results as additional supporting data for the ongoing review of the MAA.

Pfizer has worked closely with investigators and international breast cancer experts to establish a robust development program for Ibrance in HR+, HER2- breast cancer across stages and treatment settings.

PALOMA-1 is a randomized (1:1), multi-center, multinational, open label phase 2 trial designed to assess PFS in postmenopausal women with ER+, HER2- advanced breast cancer receiving Ibrance (125 mg once daily for three out of four weeks in repeated cycles) in combination with letrozole versus letrozole alone (2.5 mg once daily on a continuous regimen) as a first-line treatment. The results from PALOMA-1 were published online by The Lancet Oncology in December 2014.

PALOMA-2 is a randomized (2:1), multicenter, multinational, double-blind phase 3 study designed to assess PFS in postmenopausal women with ER+, HER2- advanced breast cancer receiving Ibrance (125 mg orally once daily for three out of four weeks in repeated cycles) in combination with letrozole (2.5 mg once daily continuously) versus letrozole plus placebo as a first-line treatment. PALOMA-2 has more than 200 global sites participating and 666 patients enrolled.

PALOMA-3 is a randomized (2:1), multicenter, multinational, double-blind phase 3 study designed to assess PFS with Ibrance (125 mg once daily orally for three out of four weeks in each cycle) in combination with fulvestrant (500 mg intramuscularly on days 1 and 15 of cycle 1, and then on day 1 of each subsequent 28 day cycle) versus fulvestrant plus placebo in pre/perimenopausal and postmenopausal women with HR+, HER2- metastatic breast cancer whose disease has progressed during or after endocrine therapy. Based on the PALOMA-3 results, a supplemental New Drug Application (sNDA) was reviewed and approved in February 2016 under the FDA’s Breakthrough Therapy designation and Priority Review programmes to expand the use of Ibrance to include use in combination with fulvestrant in women with HR+, HER2- advanced or metastatic breast cancer with disease progression following endocrine therapy.